Quantitative and qualitative changes in platelet traits of sunitinib-treated patients with renal cell carcinoma in relation to circulating sunitinib levels: a proof-of-concept study

• Published in: BMC cancer Vol. 22; no. 1; p. 653
• Main Authors: Tullemans, Bibian M E, Brouns, Sanne L N, Swieringa, Frauke, Sabrkhany, Siamack, van den Berkmortel, Franchette W P J, Peters, Natascha A J B, de Bruijn, Peter, Koolen, Stijn L W, Heemskerk, Johan W M, Aarts, Maureen J B, Kuijpers, Marijke J E
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.06.2022; BioMed Central; BMC
• Subjects: Bleeding; Blood cell count; Blood platelets; cancer; Carcinoma, Renal cell; Care and treatment; Collagen; Diagnosis; Drug dosages; Glucose; Health aspects; Hemorrhage; Kidney cancer; Medical imaging; Metastases; Metastasis; Patients; Plasma; Platelet aggregation; Platelet count; Prevention; Protein-tyrosine kinase; Renal cell carcinoma; Risk factors; Signal transduction; Sunitinib; Targeted cancer therapy; Therapeutic drug monitoring; Tyrosine kinase inhibitor; Netherlands; United States > US; Japan; Plasma; Sunitinib; Renal cell carcinoma; Tyrosine kinase inhibitor; Serum; Platelet aggregation; cancer; Patients; Bleeding; Platelet count
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09676-0

Tyrosine kinase inhibitors (TKIs), such as sunitinib, are used for cancer treatment, but may also affect platelet count and function with possible hemostatic consequences. Here, we investigated whether patient treatment with the TKI sunitinib affected quantitative and qualitative platelet traits as a function of the sunitinib level and the occurrence of bleeding. Blood was collected from 20 metastatic renal cell carcinoma (mRCC) patients before treatment, and at 2 weeks, 4 weeks and 3 months after sunitinib administration. We measured blood cell counts, platelet aggregation, and concentrations of sunitinib as well as its N-desethyl metabolite in plasma, serum and isolated platelets. Progression of disease (PD) and bleeding were monitored after 3 months. In sunitinib-treated mRCC patients, concentrations of (N-desethyl-)sunitinib in plasma and serum were highly correlated. In the patients' platelets the active metabolite levels were relatively increased as compared to sunitinib. On average, a sustained reduction in platelet count was observed on-treatment, which was significantly related to the inhibitor levels in plasma/serum. Principal component and correlational analysis showed that the (N-desethyl-)sunitinib levels in plasma/serum were linked to a reduction in both platelet count and collagen-induced platelet aggregation. The reduced aggregation associated in part with reported bleeding, but did not correlate to PD. The sunitinib-induced reduction in quantitative and qualitative platelet traits may reflect the effective sunitinib levels in the patient. These novel results may serve as a proof-of-principle for other TKI-related drugs, where both platelet count and functions are affected, which could be used for therapeutic drug monitoring.